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Int J Mol Med ; 45(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789424

RESUMO

Oxidative and inflammatory damage has been suggested to play important roles in the pathogenesis of skin photoaging. Andrographolide sodium bisulfate (ASB) is a soluble derivative of andrographolide and has known antioxidant and anti­inflammatory properties. In the present study, cellular experiments were designed to investigate the molecular mechanisms underlying the effect of ASB in relieving ultraviolet (UV)­induced photo­damage. Following ASB pretreatment and UV irradiation, the apoptosis and necrosis of HaCaT cells were investigated by Hoechst 33342/propidium iodide staining. Reactive oxygen species (ROS) production was investigated using a DCFH­DA fluorescence probe. Furthermore, the protein expression levels of p65, NF­κB inhibitor­α, nuclear factor E2­related factor 2 (Nrf2) and kelch­like ECH­associated protein 1 (keap1) were measured via western blotting and immunofluorescence analyses. Furthermore, NF­κB­mediated cytokines were assessed by ELISA, and Nrf2­mediated genes were detected by reverse transcription­quantitative PCR. Pretreatment with ASB markedly increased cell viability, decreased cell apoptosis and decreased UV­induced excess ROS levels. In addition, ASB activated the production of Nrf2 and increased the mRNA expression levels of glutamate­cysteine ligase catalytic subunit and NAD(P)H quinone oxidoreductase 1, while ASB downregulated the protein expression of p65 and decreased the production of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α. These results suggested that ASB attenuates UV­induced photo­damage by activating the keap1/Nrf2 pathway and downregulating the NF­κB pathway in HaCaT keratinocytes.

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